Study On The Binding And Stabilization Of Ruthenium(?) Complexes On Triplex RNA

RNA can form complex secondary and tertiary structures.The RNA triplex is an important tertiary motif,which is found in many pseudoknots and other structures of RNA.More than 60 years ago,Gary Felsenfeld et al.first observed the RNA triplex in vitro,but the biological activity of the triple helix structure has only just begun to attract attention.There is abundant evidence that they may be involved in a variety of biological processes,including transcriptional regulation,post-transcriptional RNA processing,chromatin modification,and DNA repair.In general,the stability of RNA triplex is the key factor affecting their application in physiological conditions.However,due to Hoogsteen base pairing,the triplex is less stable than the corresponding parent duplex,which limits their practical application.Therefore,how to improve the stability of triplex RNA is an urgent problem to be solved.In this regard,there is a great demand for small molecules that can recognize,bind,and stabilize specific sequences of the triplex.Taking into account the outstanding advantages of ruthenium complexes in the field of targeted DNA research,our group has been working for nearly a decade to design highly modular ruthenium(II)complexes and to study their binding behavior when targeting triplex RNA.Therefore,the binding behavior of some modular ruthenium complexes to triple helical RNA was systematically designed and studied using a variety of biophysical techniques.In this paper,the basic knowledge of tri-helix nucleic acids is firstly reviewed,including the definition,structure,formation mode,classification system,biological significance and common binding agents of triple-helical nucleic acids.Previous studies by Barton,Nordén and Ji Liangnian,academician of China,showed that the chiral ruthenium(II)complexes exhibit significant enantioselectivity in targeting DNA.In this study,two chiral ruthenium(II)complexes with different electronic properties of substituents on the main ligand were synthesized and their interactions with triple helical RNA were studied.Results show that compared with?-enantiomers,?-enantiomers with triplex RNA has a stronger affinity,have a more stable effect on the triplex RNA.Then,we investigate the important role of the difference between the substituent electron effect and the ancillary ligand effect on the dppz group in the targeting of the Ru(II)complex to the triplex RNA.The results show that the complexes with strong electron absorption and greater hydrophobicity are excellent stabilizers.Second,studies have shown that not only intercalators can act as stabilizers of triplex RNA.For example,we recently reported several highly charged cationic Ru(II)polypyridyl metal peptide complexes rich in lysine,glycine and arginine,which are driven by hydrogen bonds,electrostatic interactions,and hydrophobic interactions to bind to the triplex and significantly improve the stability of triplex RNA.In addition,a novel highly water-soluble Ru(II)complex[Ru(phen)₂L']²⁺containing macrocyclic polyamine units was considered to be able to cleave DNA plasmids effectively during photoactivation.Therefore,the stabilization effect of macrocyclic polyamine ligands and their complexes based on bipyridine unit on triple helical RNA was studied.The results show that the introduction of macrocyclic ligands to the parent complex can significantly improve the stability of the triplex.Finally,the effect of the position difference of-CN substituents on the stability of the triplex RNA was studied.The results show that the complexes with ortho-cyanide group are more stable to the triplex RNA.